Human pathogenic viruses are a kind of nucleic acid particles with very simple structure. Most of them lack of enzymatic system, and they have to depend on the host cells to replicate their nucleic acids and proteins and then assemble into virus particles so that the viruses are replicated. Virus infection can cause various diseases and threaten the human health and lives severely. At present, the viruses with high morbidity and great harmfulness mainly include influenza virus, hepatitis B virus, AIDS virus, cytomegalovirus and herpes virus, etc.
Now in the treatment of viral diseases, there still lack of drugs of high specificity, and the common drugs used in clinical mainly are divided into the following types: the antiviral drugs for inhibiting the virus replication; the immunomodulators for enhancing the body's immune function; the antitussive, anodyne, antipyretic and antipyrotic drugs and the like against clinical symptom; the anti-infection drugs for preventing secondary infection; the vaccines for preventing virus infection and the disinfectants for blocking the transmission of viruses, etc.
At present, the study of new drugs for treatment of viral diseases is highlighted on the antiviral drugs. The widely used anti-influenza virus drugs include the adamantanamine drugs, the neuramidinase inhibitors of influenza virus, the receptor blocking agent of influenza virus and the antisense oligonucleotide against influenza virus etc. And the ones used clinically mainly are the adamantanamine drugs and the neuramidinase inhibitors. However, the hepatitis virus infection is recognized as an international therapeutic problem so far.
In 1980's, the vidarabine, vidarabine phosphate, acyclovir, zidovudine have been studied. However, they are not used to treat hepatitis now due to their poor therapeutic effect and strong toxic reaction. In recent years, many nucleoside drugs, such as lamivudine, famciclovir, lobucavir, adefovir dipivoxiil, FTC (dideoxyfluorinethiocytosine), FMAU (fluoro-methylarabinosyluracil), FDDC (fluoro-dideoxycytosine), BMS 200475 (epoxyhydroxylcarbodeoxy guanosine), have been developed by screening the drugs against hepatitis B virus and hepatitis C virus with the established hepatoma carcinoma cell lines, hepatitis virus transfected cell lines or transgenic cell lines, and transgenic mouse hepatitis animal model, they have obvious inhibiting activities to HBV. More than 30 kinds of drugs were carried out the preclinical trial research by the researchers in 1998-2002. And there are 21 drugs entering the stage II-III clinical trial recently. Among these trial drugs, the ones for anti hepatitis B virus are mostly the anti HIV revertase inhibitors and anti-herpes virus DNA polymerase inhibitors. Among other things, enticavir have entered stage III clinical trial, and may go on the market soon. The trial drugs for anti hepatitis C virus are mostly the broad spectrum antiviral drugs or RNA virus inhibitors, and the immunomodulators having antiviral activity.
At present, most of the approved antiviral drugs are nucleoside compounds. In the course of clinical uses, they have been found to have the following disadvantages: 1) cytotoxicity; 2) occurrence of drug resistant virus variants induced by long-term medication to which other drugs having different structure are need. Therefore, the non-nucleoside antiviral drugs became an aspect catching much attention.